Identification of candidate circulating cisplatin-resistant biomarkers from epithelial ovarian carcinoma cell secretomes

P. N. Teng, G. Wang, B. L. Hood, K. A. Conrads, C. A. Hamilton, G. L. Maxwell, K. M. Darcy*, T. P. Conrads

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Background:The majority of patients diagnosed with advanced epithelial ovarian carcinoma (EOC) relapse with resistant disease, and there are no biomarkers that possess clinical utility to identify or monitor these patients. This study aimed to identify secreted proteins ('secretome') collected from human EOC cell lines that differ in their inherent platinum sensitivity.Methods: Secreted proteins collected from conditioned medium from ovarian cancer cell lines that vary in their sensitivity to cisplatin were digested with trypsin and analysed by liquid chromatography-tandem mass spectrometry for peptide identification.Results:Of the 1688 proteins identified, 16 possessed significant differential abundances (P<0.05) between the platinum-resistant and-sensitive cell lines. A number of these were verified by immunoblot, including COL11A1, which was also found to be associated with worse progression-free survival (PFS; N=723) and overall survival (OS; N=1183) as assessed from publicly available transcript expression data from ovarian cancer tumour specimens.Conclusion:Secretome proteomics of EOC cells resulted in the identification of a novel candidate biomarker, COL11A1. The expression level of COL11A1 correlates to worse PFS and OS, and is predicted to reside in peripheral circulation making this an attractive candidate for validation in sera as a biomarker of cisplatin resistance and poor outcome.

Original languageEnglish
Pages (from-to)123-132
Number of pages10
JournalBritish Journal of Cancer
Volume110
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • biomarker
  • cisplatin resistance
  • ovarian cancer
  • proteomics
  • secretome

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